Digital health technologies are rapidly transforming prescription therapies from traditional chemical compounds into integrated software-and-drug health systems. As mobile applications and connected devices increasingly accompany pharmaceuticals, life science companies face a complex regulatory matrix. To clarify these boundaries, the FDA issued a new guidance outlining how drug labeling authorities apply to Prescription Drug Use-Related Software (PDURS). Understanding where software output falls, whether as FDA-required labeling or promotional material, is now critical for regulatory compliance and product positioning. Sponsors must comply with FDA’s core recommendations for companion software.
The FDA guidance establishes a risk-based, evidence-driven framework for regulating software functions disseminated by or on behalf of drug sponsors for use with prescription drugs or CDER/CBER-led combination products. The guidance applies specifically to software disseminated by or on behalf of a drug sponsor that produces end-user output, such as screens, dynamic displays, or audio alerts, textually related to the sponsor’s drug product.
The FDA classifies software functions into two primary operational categories. Device-Connected Functions where the software functions rely on data directly transferred from a device or device constituent part of a combination product (e.g., a smart autoinjector or connected inhaler), or Standalone Functions where the software does not receive direct device data, but relies on manual patient data entry or general health tracking.
The FDA treats end-user software outputs as a form of prescription drug labeling. The Agency categorizes these outputs based on clinical evidence and utility. End-user outputs and software descriptions belong in the Prescribing Information (PI) if the software is determined essential for the safe and effective use of the drug, or if the sponsor provides clinical evidence from adequate and well-controlled studies showing that the software leads to a meaningful improvement in a clinical outcome. In such cases, clinical results are detailed in the Clinical Studies section of the PI, and post-approval changes to the output generally require formal FDA review and approval prior to implementation.
If software is optional and does not demonstrate a meaningful improvement in clinical outcomes, its end-user output is treated as promotional labeling. For device-connected functions, sponsors may include a brief factual description of the device connectivity in the How Supplied/Storage and Handling section of the PI, accompanied by an explicit statement that the software is not necessary for safe and effective drug use. Standalone software functions lacking clinical outcome evidence or safety necessity should generally not be mentioned in the PI at all.
For software output classified as promotional labeling, sponsors must submit the materials to the FDA using Form FDA 2253 at the time of initial dissemination. Crucially, routine software updates that do not alter the end-user output (such as technical security patches or operating system compatibility updates) do not require re-submission. Furthermore, sponsors modifying software functions that meet the statutory definition of a medical device must continue to adhere to CDRH device premarket requirements in addition to drug labeling obligations.
As digital health technologies become deeply intertwined with modern medicine, drug sponsors must approach software development with regulatory labeling in mind. Differentiating early between device-connected and standalone software functions enables teams to map out exact clinical evidence requirements and postmarket obligations. Early alignment with CDER or CBER review divisions remains the single best strategy for generating robust clinical evidence capable of elevating companion apps into approved drug labeling. By treating digital interfaces with the same regulatory rigor as physical drug delivery systems, life science companies can maximize therapeutic value while staying fully compliant. Ultimately, navigating this guidance effectively allows sponsors to transform digital health innovation into a true competitive and clinical advantage.
